Disparities between Asian and Non-Asian Thrombolyzed Acute Ischemic Stroke Patients in the Enhanced Control of Hypertension and Thrombolysis Stroke Trial.

BACKGROUND AND PURPOSE: As outcomes for acute ischemic stroke (AIS) vary according to clinical profile and management approaches, we aimed to determine disparities in clinical outcomes between Asian and non-Asian participants of the international, Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED). METHODS: ENCHANTED was a multicenter, prospective, partial-factorial, randomized, open trial of low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) alteplase, and intensive (target systolic blood pressure [SBP] 130-140 mm Hg) or guideline-recommended (<180 mm Hg) BP management, in thrombolysis-eligible AIS patients. Logistic regression models were used to examine the associations with outcomes of death or disability (modified Rankin scale [mRS] scores 2-6), major disability (mRS 3-5), death, and intracranial hemorrhage (ICH), with adjustment prognostic factors, alteplase dose, and mean SBP over 1-24 h. RESULTS: Among 4,551 thrombolyzed AIS patients (mean age 66.7 years, 37.8% female), there were 65.4% Asians who were younger, fewer female, and with less atrial fibrillation, hypercholesterolemia, premorbid symptoms, and concomitant antihypertensive, antithrombotic and statin treatment, and more prior stroke, compared to non-Asians. Frequencies of hypertension, coronary artery disease, and diabetes mellitus were comparable between groups. Asian patients were less likely to be admitted to an acute stroke unit and receive early mobilization by a therapist or rehabilitation but more likely to receive intensive care. There were no significant differences between Asians and non-Asians in functional outcome (defined by mRS scores 2-6 or 3-5; adjusted odds ratio [OR] 1.00, 95% confidence interval [CI] 0.85-1.19 [p = 0.958] and OR 0.95, 95% CI 0.80-1.13 [p = 0.572], respectively), or death (OR 1.25, 95% CI 0.95-1.65; p = 0.116), despite Asians having greater odds of ICH (OR 1.51, 95% CI 1.23-1.86; p = 0.0001) and neurological deterioration within 24 h (OR 1.58, 95% CI 1.18-2.12; p = 0.002). CONCLUSIONS: Within the context of an international clinical trial of thrombolyzed AIS patients, demography, risk factors, management, and odds of early neurological deterioration and ICH, all differ between Asian and non-Asian participants. However, patterns of functional recovery are similar between these major regional groups.

Non-vitamin K antagonist oral anticoagulants in very elderly east Asians with atrial fibrillation: A nationwide population-based study.

BACKGROUND: The evidence of effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) among elderly East Asians is limited. OBJECTIVES: We aimed to describe the effectiveness and safety outcomes associated with NOACs and warfarin among elderly Koreans aged ≥80 years. METHODS: Using the Korean Health Insurance Review and Assessment service database, patients with atrial fibrillation (AF) who were naïve to index oral anticoagulant between 2015 and 2017 were included in this study (20,573 for NOACs and 4086 for warfarin). Two treatment groups were balanced using the inverse probability of treatment weighting (IPTW) method. The clinical outcomes including ischemic stroke, major bleeding including intracranial hemorrhage (ICH) and gastrointestinal bleeding (GIB), and a composite of these outcomes were evaluated. RESULTS: Compared to warfarin, NOACs were associated with lower risks of ischemic stroke (hazard ratio 0.74 [95% confidence interval 0.62-0.89]), and composite outcome (0.78 [0.69-0.90]). NOACs showed nonsignificant trends towards to lower risks of GIB and major bleeding than warfarin. The risk of ICH of NOAC group was comparable with the warfarin group. Among NOACs, apixaban and edoxaban showed better composite outcomes than warfarin. Among the clinical outcomes, only ischemic stroke and the composite outcome had a significant interaction with age subgroups (80-89 years and ≥90 years, P-for-interaction = .097 and .040, respectively). CONCLUSION: NOACs were associated with lower risks of ischemic stroke and the composite outcome (ischemic stroke and major bleeding) compared to warfarin in elderly East Asians. Physicians should be more confident in prescribing NOACs to elderly East Asians with AF.

Predictors and prognoses of new onset post-stroke anxiety at one year in black Africans.

BACKGROUND: There is relatively limited information on the risk factors and outcome of new onset Poststroke Anxiety (PSA) in Low- and Middle-Income Countries. We estimated incidence, cumulative incidence, risk factors and outcome of new onset anxiety in the first year of stroke among African stroke survivors. METHODS: We analyzed the dataset of a completed clinical trial comprising patients enrolled to test an intervention designed to improve one-year blood pressure control among recent (≤ one month) stroke survivors in Nigeria. Anxiety was measured using the Hospital Anxiety and Depression Scale. Outcomes were assessed using the modified Rankin Scale (mRS), Community screening instrument for dementia (CSID) and Health Related Quality of Life in Stroke Patients (HRQOLISP-26). RESULTS: Among 322 stroke survivors who were free of anxiety at baseline, we found a one-year cumulative incidence of 34% (95% CI = 28.6-39.3). Rates were 36.2% (95% CI =29.6-42.7) for men and 29.2% (95% CI =19.9-38.3) for women. In multivariate Cox regression analyses, haemorrhagic stroke type was associated with higher risk of new onset PSA (Hazard Ratio=1.52, 95% CI =1.01-2.29). New onset PSA was independently associated with cognitive [(mean difference (MD) in CSID scores=1.1, 95% C.I=0.2, 1.9)] and motor decline (MD in mRS scores= -0.2, 95% C.I= -0.4, -0.02), as well as poorer quality of life overtime (MD in total HRQOLISP-26 scores=3.6, 95% C.I=1.0, 6.2). CONCLUSION: One in 3 stroke survivors in Nigeria had PSA at one year. Clinicians in SSA should pay special attention to survivors of haemorrhagic stroke as they are at higher risk of incident anxiety and therefore its consequences.

Rates of Intracranial Hemorrhage in Mild Head Trauma Patients Presenting to Emergency Department and Their Management: A Comparison of Direct Oral Anticoagulant Drugs with Vitamin K Antagonists.

Background and objectives: Anticoagulants are thought to increase the risks of traumatic intracranial injury and poor clinical outcomes after blunt head trauma. The safety of using direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKAs) after intracranial hemorrhage (ICH) is unclear. This study aims to compare the incidence of post-traumatic ICH following mild head injury (MHI) and to assess the need for surgery, mortality rates, emergency department (ED) revisit rates, and the volume of ICH. Materials and Methods: This is a retrospective, single-center observational study on all patients admitted to our emergency department for mild head trauma from 1 January 2016, to 31 December 2018. We enrolled 234 anticoagulated patients, of which 156 were on VKAs and 78 on DOACs. Patients underwent computed tomography (CT) scans on arrival (T0) and after 24 h (T24). The control group consisted of patients not taking anticoagulants, had no clotting disorders, and who reported an MHI in the same period. About 54% in the control group had CTs performed. Results: The anticoagulated groups were comparable in baseline parameters. Patients on VKA developed ICH more frequently than patients on DOACs and the control group at 17%, 5.13%, and 7.5%, respectively. No significant difference between the two groups was noted in terms of surgery, intrahospital mortality rates, ED revisit rates, and the volume of ICH. Conclusions: Patients with mild head trauma on DOAC therapy had a similar prevalence of ICH to that of the control group. Meanwhile, patients on VKA therapy had about twice the ICH prevalence than that on the control group or patients on DOAC, which remained after correcting for age. No significant difference in the need for surgery was determined; however, this result must take into account the very small number of patients needing surgery.

Comparison of Clinical Care and In-Hospital Outcomes of Asian American and White Patients With Acute Ischemic Stroke.

Importance: Although overall stroke incidence and mortality in the United States is improving, little is known about the characteristics and clinical outcomes of acute ischemic stroke in Asian American individuals. Objective: To compare the characteristics, care, and outcomes of Asian American and white patients with acute ischemic stroke. Design, Setting, Participants: Retrospective analysis of Asian American and white patients admitted with a primary diagnosis of acute ischemic stroke to hospitals participating in the Get With The Guidelines-Stroke (GWTG-Stroke) program between April 1, 2004, and July 31, 2016. The GWTG-Stroke database is a prospectively collected stroke quality improvement registry sponsored by the American Heart Association/American Stroke Association. Main Outcomes and Measures: Multivariable logistic regression models assessed the association of Asian American race/ethnicity, clinical outcomes, and quality measures. Results: The study population of 1 772 299 patients (mean [SD] age, 72.4 [14.2] years; 51.3% female) consisted of 64 337 Asian American patients (3.6%) and 1 707 962 white patients (96.4%) admitted to 2171 GWTG-Stroke hospitals with acute ischemic stroke. After adjustment for patient and hospital variables, Asian American patients were seen with greater stroke severity compared with white patients (National Institutes of Health Stroke Scale [NIHSS] score ≥16) (odds ratio [OR], 1.35; 95% CI, 1.30-1.40; P < .001), manifested higher in-hospital mortality (OR, 1.14; 95% CI, 1.09-1.19; P < .001), had longer length of stay (OR, 1.17; 95% CI, 1.14-1.20; P < .001), and were less likely to ambulate independently at discharge (OR, 0.84; 95% CI, 0.79-0.90; P < .001). Although Asian American patients had fewer intravenous tissue plasminogen activator (IV tPA) administrations than white patients (OR, 0.95; 95% CI, 0.91-0.98; P = .003), they had more symptomatic hemorrhage after tPA (OR, 1.36; 95% CI, 1.20-1.55; P < .001) and overall post-tPA complications (OR, 1.31; 95% CI, 1.18-1.46; P < .001). Asian American patients had better quality measure adherence overall than white patients, including rehabilitation (OR, 1.27; 95% CI, 1.18-1.36; P < .001), door to tPA within 60 minutes (OR, 1.14; 95% CI, 1.06-1.22; P < .001), and intensive statin therapy (OR, 1.14; 95% CI, 1.10-1.18; P < .001). After adjustment for stroke severity, Asian American patients had lower in-hospital mortality than white patients (OR, 0.95; 95% CI, 0.91-0.99; P = .008). Conclusions and Relevance: Asian American patients manifested more severe ischemic strokes, were less likely to receive IV tPA, and had worse functional outcomes than white patients. These findings warrant additional research toward improving clinical outcomes for Asian American patients with acute ischemic stroke.

Clinical outcomes, edoxaban concentration, and anti-factor Xa activity of Asian patients with atrial fibrillation compared with non-Asians in the ENGAGE AF-TIMI 48 trial.

AIMS: Prior studies suggested that the risks of ischaemic stroke and bleeding in patients of Asian race with atrial fibrillation (AF) may be higher than that of non-Asians. In the analysis of ENGAGE AF-TIMI 48 trial, we compared clinical outcomes, edoxaban concentration, and anti-factor Xa (anti-FXa) activity, between Asian and non-Asian races. METHODS AND RESULTS: There were 2909 patients of Asian race and 18 195 non-Asian race in the ENGAGE AF-TIMI 48 trial. The risks of thromboembolism and bleeding events were compared for Asians and non-Asians treated with warfarin. The trough levels of edoxaban concentration and anti-FXa activity were also compared and correlated with the efficacy and safety of edoxaban vs. warfarin. Compared to non-Asian patients, the Asian population was on average 2 years younger and 20 kg lighter. In the warfarin group, the adjusted risk of ischaemic stroke did not differ significantly for patients of Asian and non-Asian race [adjusted hazard ratio (aHR) = 1.12, P = 0.56). Asians treated with warfarin had a higher-adjusted risk of intracranial haemorrhage (ICH: aHR 1.71, P = 0.03) compared with non-Asians. The trough edoxaban concentration and anti-FXa activity were 20-25% lower for Asians compared with non-Asians. Compared to warfarin, higher dose edoxaban significantly reduced ICH while preserving the efficacy of stroke prevention in both Asians and non-Asians. Two of three net clinical outcomes appeared to be more favourably reduced with edoxaban in Asians compared with non-Asians (Pint = 0.063 for primary, 0.037 for secondary, and 0.032 for third net clinical outcomes, respectively). CONCLUSION: Compared to warfarin, higher dose edoxaban preserved the efficacy for stroke prevention and was associated with a favourable safety profile for Asians, which may be due to the lower trough edoxaban concentration and anti-FXa activity achieved in patients of Asian race.

The Risk of Hemorrhagic Transformation After Thrombolysis for Acute Ischemic Stroke in Chinese Versus North Americans: A Comparative Study.

BACKGROUND: There is a widespread belief that Asians are more susceptible to hemorrhagic transformation (HT) after receiving recombinant tissue-type plasminogen activator (rt-PA) for acute ischemic stroke (AIS). However, this has not been examined in clinical practice. This study aims to compare the incidence of symptomatic hemorrhagic transformation (SHT) among thrombolysis-treated AIS patients in China and in the United States. METHODS: We compared 212 consecutive patients receiving thrombolysis within 4.5 hours of onset ± endovascular therapy from an American (n = 86) and a Chinese Stroke Center (n = 126). SHT was defined using various definitions based on the National Institute for Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator (NINDS rt-PA) trials, European-Australian Cooperative Acute Stroke Study 2 (ECASS2), and a modified version of Safe Implementation of Thrombolysis in Stroke-Monitoring Study (mSITS-MOST) study criteria. We used Firth logistic regression to adjust for confounding variables and to identify potential predictors. RESULTS: American patients were older, and had higher prevalence of diabetes, hypertension, cardiac disease, and prestroke use of antithrombotics. They also had higher baseline serum glucose, shorter onset-to-treatment time, and fewer endovascular treatments. The rates of SHT were higher in the American cohort compared to the Chinese cohort: 18.6% versus 14.3% based on NINDS definition of SHT; 15.1% versus 12.7% based on ECASS2; and 11.6% versus 7.2% based on mSITS-MOST. However, none of these differences were significant (unadjusted and adjusted P values > .05). Fatal HT was comparable in Americans versus Chinese (8.1% versus 8.7%). Serum glucose emerged as an independent predictor of SHT (P = .024). CONCLUSIONS: In our cohorts, the rate of SHT after thrombolysis is equivalent between Chinese and North American stroke patients.

Causes of Death in Different Subtypes of Ischemic and Hemorrhagic Stroke.

Causes of death in both ischemic stroke (IS) and hemorrhagic stroke (HS) subtypes are not comprehensively studied. Between 2008 and 2011, we enrolled 11 215 first-ever stroke patients from the Stroke Registry of Chang-Gung Healthcare System and linked these data to the national death registry. The main causes of death in each stroke subtype were assessed. Patients with HS had higher overall mortality than IS (32.0% vs 18.1%, P < .001). In IS subtypes, large-artery atherosclerosis plus cardioembolism had the worst mortality (40.7%, P < .001). Stroke was the leading cause of death in both IS and HS within the first year. Stroke remained the major cause of death in HS, but cancer was the leading cause of death in IS after the first year. After excluding the patients with previous cancer history, cancer was still an important cause of death in IS and HS, particularly in the IS subtypes of small vessel occlusion, stroke of undetermined etiology, and transient ischemic attack.

Cohort Study of ECG Left Ventricular Hypertrophy Trajectories: Ethnic Disparities, Associations With Cardiovascular Outcomes, and Clinical Utility.

BACKGROUND: ECG left ventricular hypertrophy (LVH) is a well-known predictor of cardiovascular disease. However, no prior study has characterized patterns of presence/absence of ECG LVH ("ECG LVH trajectories") across the adult lifespan in both sexes and across ethnicities. We examined: (1) correlates of ECG LVH trajectories; (2) the association of ECG LVH trajectories with incident coronary heart disease, transient ischemic attack, ischemic stroke, hemorrhagic stroke, and heart failure; and (3) reclassification of cardiovascular disease risk using ECG LVH trajectories. METHODS AND RESULTS: We performed a cohort study among 75 412 men and 107 954 women in the Northern California Kaiser Permanente Medical Care Program who had available longitudinal exposures of ECG LVH and covariates, followed for a median of 4.8 (range <1-9.3) years. ECG LVH was measured by Cornell voltage-duration product. Adverse trajectories of ECG LVH (persistent, new development, or variable pattern) were more common among blacks and Native American men and were independently related to incident cardiovascular disease with hazard ratios ranging from 1.2 for ECG LVH variable pattern and transient ischemic attack in women to 2.8 for persistent ECG LVH and heart failure in men. ECG LVH trajectories reclassified 4% and 7% of men and women with intermediate coronary heart disease risk, respectively. CONCLUSIONS: ECG LVH trajectories were significant indicators of coronary heart disease, stroke, and heart failure risk, independently of level and change in cardiovascular disease risk factors, and may have clinical utility.

ESR2 Genetic Variants and Combined Oral Contraceptive Use Associated with the Risk of Stroke.

BACKGROUND AND AIM: There is accumulating evidence suggesting an important role of estrogen receptor-ß in the development of cardiovascular disease. The present study aims to investigate the relationship of estrogen receptor ß gene (ESR2) polymorphisms with stroke risk in Chinese women, and further evaluate the gene-environment interaction of ESR2 and combined oral contraceptive (COC) use on stroke risk. METHODS: A case-control study was conducted with 446 first-ever stroke patients and 864 control subjects recruited from our prospective female cohort. Four polymorphisms of ESR2 gene were genotyped, and the information of contraceptive use was obtained by a face-to-face interview. RESULTS: Women with rs1256065 CC genotype were at a 1.59 fold increased risk of stroke. Subtype analyses showed that the risk genotype of rs1256065 was associated with ischemic stroke, but not with hemorrhagic stroke. AA genotype of rs4986938 showed a significant correlation with an elevated risk of hemorrhagic stroke. COC users with rs1256065 CC genotype had a 2.36 fold increased risk of stroke, compared with the non-users with the wild-type genotype. Moreover, a significant multiplicative interaction on hemorrhagic stroke was detected between COC use and rs4986938 (pinteraction = 0.023). The risk of hemorrhagic stroke was significantly elevated among carriers of rs4986938 GA or AA genotype combined with COC use. No associations were observed for rs1256049 and rs1271572. CONCLUSIONS: ESR2 genetic polymorphisms were associated with the risk of first-ever stroke in Chinese women, and the AA genotype of rs4986938 combined with COC use could significantly increase the risk of hemorrhagic stroke.

Fine Particulate Matter (PM2.5) and the Risk of Stroke in the REGARDS Cohort.

BACKGROUND: Ambient particulate matter has been shown to be associated with declining human health, although the association between fine particulate matter (PM2.5) and stroke is uncertain. METHODS: We utilized satellite-derived measures of PM2.5 to examine the association between exposure and stroke in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. We used a time-stratified case-crossover design, with exposure lags of 1 day, 2 days, and 3 days. We examined all strokes, as well as ischemic and hemorrhagic strokes separately. RESULTS: Among 30,239 participants in the REGARDS study, 746 incident events were observed: 72 hemorrhagic, 617 ischemic, and 57 of unknown type. Participants exposed to higher levels of PM2.5 more often resided in urban areas compared to rural, and in the southeastern United States. After adjustment for temperature and relative humidity, no association was observed between PM2.5 exposure and stroke, regardless of the lag (1-day lag OR = .99, 95% CI: .83-1.19; 2-day lag OR = .95, 95% CI: .80-1.14; 3-day lag OR = .95, 95% CI = .79-1.13). Similar results were observed for the stroke subtypes. CONCLUSIONS: In this large cohort of African-Americans and whites, no association was observed between PM2.5 and stroke. The ability to examine this association with a large number of outcomes and by stroke subtype helps fill a gap in the literature examining the association between PM2.5 and stroke.

Dietary antioxidant capacity and risk for stroke in a prospective cohort study of Swedish men and women.

OBJECTIVE: Both observational studies and randomized trials have shown that a diet rich in antioxidants can reduce systemic inflammation and oxidative stress, two conditions that, together with obesity and smoking, are established risk factors for stroke. However, the association between antioxidant intake and risk for stroke is poorly understood, particularly when studying possible interaction with sex. We investigated the relationship of nonenzymatic antioxidant capacity (NEAC) on risk for stroke in a large Swedish prospective cohort. METHODS: The cohort study included 34 555 men and women from the Swedish National March Cohort. NEAC was assessed using a detailed food frequency questionnaire, collected at baseline. We achieved complete follow-up from enrollment in 1997 through 2010 by record linkage to nationwide registers. We identified 1186 incident cases of a first stroke, of which 860 were ischemic, 201 hemorrhagic, and 125 unspecified. We used multivariable Cox proportional hazards models to estimate adjusted hazard ratios (HR) with 95% confidence intervals (CIs). RESULTS: Compared with women in the lowest quartile of NEAC, women in the highest quartile had a 27% lower incidence of total stroke (HR, 0.73; 95% CI, 0.53-0.99; Ptrend = 0.03) and 35% lower incidence of ischemic stroke (HR, 0.65; 95% CI, 0.43-0.99; Ptrend = 0.01). Among men, the relationship between NEAC and risk for stroke was not statistically significant and all HRs were close to unity. CONCLUSION: Findings from the present study suggest that dietary antioxidant capacity from different foods and beverages is inversely associated with risk for stroke, more specifically ischemic stroke, in women.

High rate of microbleed formation following primary intracerebral hemorrhage.

BACKGROUND: We sought to investigate the frequency of microbleed development following intracerebral hemorrhage in a predominantly African-American population and to identify predictors of new microbleed formation. AIMS AND/OR HYPOTHESIS: To investigate the frequency and predictors of new microbleeds following intracerebral hemorrhage. METHODS: The DECIPHER study was a prospective, longitudinal, magnetic resonance-based cohort study designed to evaluate racial/ethnic differences in risk factors for microbleeds and to evaluate the prognostic impact of microbleeds in this intracerebral hemorrhage population. We evaluated new microbleed formation in two time periods: from baseline to 30 days and from 30 days to year 1. RESULTS: Of 200 subjects enrolled in DECIPHER, 84 had magnetic resonance imaging at all required time points to meet criteria for this analysis. In the baseline to day 30 analysis, 11 (13·1%) had new microbleeds, compared with 25 (29·8%) in the day 30 to year 1 analysis. Logistic regression analysis demonstrated that baseline number of microbleeds [odds ratio 1·05 (95% confidence interval 1·01, 1·08), P = 0·01] was associated with new microbleed formation at 30 days. A logistic regression model predicting new microbleed at one-year included baseline number of microbleeds [odds ratio 1·05 (1·00, 1·11), P = 0·046], baseline age [odds ratio 1·05 (1·00, 1·10), P = 0·04], and white matter disease score [odds ratio 1·18 (0·96, 1·45). P = 0·115]. Overall, 28 of 84 (33·3%) intracerebral hemorrhage subjects formed new microbleeds at some point in the first year post-intracerebral hemorrhage. CONCLUSIONS: We found that one-third of intracerebral hemorrhage subjects in this cohort surviving one-year developed new microbleeds, which suggests a dynamic and rapidly progressive vasculopathy. Future studies are needed to examine the impact of new microbleed formation on patient outcomes.

Relationship between stroke and mortality in dialysis patients.

BACKGROUND AND OBJECTIVES: Stroke is common in patients undergoing long-term dialysis, but the implications for mortality after stroke in these patients are not fully understood. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A large cohort of dually-eligible (Medicare and Medicaid) patients initiating dialysis from 2000 to 2005 and surviving the first 90 days was constructed. Medicare claims were used to ascertain ischemic and hemorrhagic strokes occurring after 90-day survival. A semi-Markov model with additive hazard extension was generated to estimate the association between stroke and mortality, to calculate years of life lost after a stroke, and to determine whether race was associated with differential survival after stroke. RESULTS: The cohort consisted of 69,371 individuals representing >112,000 person-years of follow-up. Mean age±SD was 60.8±15.5 years. There were 21.1 (99% confidence interval [99% CI], 20.0 to 22.3) ischemic strokes and 4.7 (99% CI, 4.2 to 5.3) hemorrhagic strokes after cohort entry per 1000 patient-years. At 30 days, mortality was 17.9% for ischemic stroke and 53.4% for hemorrhagic stroke. The adjusted hazard ratio (AHR) depended on time since entry into the cohort; for patients who experienced a stroke at 1 year after cohort entry, for example, the AHR of hemorrhagic stroke for mortality was 25.4 (99% CI, 22.4 to 28.4) at 1 week, 9.9 (99% CI, 8.4 to 11.6) at 3 months, 5.9 (99% CI, 5.0 to 7.0) at 6 months, and 1.8 (99% CI, 1.5 to 2.1) at 24 months. The corresponding AHRs for ischemic stroke were 11.7 (99% CI, 10.2 to 13.1) at 1 week, 6.6 (99% CI, 6.4 to 6.7) at 3 months, and 4.7 (99% CI, 4.5 to 4.9) at 6 months, remaining significantly >1.0 even at 48 months. Median months of life lost were 40.7 for hemorrhagic stroke and 34.6 for ischemic stroke. For both stroke types, mortality did not differ by race. CONCLUSIONS: Dialysis recipients have high mortality after a stroke with corresponding decrements in remaining years of life. Poststroke mortality does not differ by race.

Race/Ethnic differences in the risk of hemorrhagic complications among patients with ischemic stroke receiving thrombolytic therapy.

BACKGROUND AND PURPOSE: Race/ethnic-related differences in safety of intravenous thrombolytic therapy have been shown in patients with myocardial infarction, but not studied in ischemic stroke. METHODS: Using data from the Get With The Guidelines (GWTG)-Stroke program (n=54 334), we evaluated differences in risk-adjusted bleeding rates (any, symptomatic intracerebral hemorrhage [sICH], serious life-threatening [excluding sICH], or other) and mortality in white (n=40 411), black (n=8243), Hispanic (n=4257), and Asian (n=1523) patients receiving intravenous tissue-type plasminogen activator (tPA) for acute ischemic stroke. RESULTS: Compared with white patients, overall adjusted hemorrhagic complications after tPA were higher in black (odds ratio, 1.14, 95% confidence interval, 1.04-1.28) and Asian (odds ratio, 1.36, 95% confidence interval, 1.14-1.61) patients. Overall adjusted bleeding complications in Hispanics were similar to those of whites. Increased risk of overall bleeding in Asians was related to higher risk of adjusted sICH (odds ratio, 1.47, 95% confidence interval, 1.19-1.82), whereas in blacks, it was related to higher risk of other bleeding. No significant race-related difference was noted in risk of serious or life-threatening bleeding or in overall mortality or death in patients with sICH or any hemorrhagic complications. CONCLUSIONS: In patients with stroke receiving tPA, hemorrhagic complications were slightly higher in blacks and Asians, but not in Hispanics compared with whites. Asians also faced significantly higher risk for sICH relative to other race/ethnic groups. Future studies are needed to evaluate whether reduction in tPA dose similar to that used in many Asian countries could improve the safety of tPA therapy in Asians in the United States with acute ischemic strokes while maintaining efficacy.

Racial differences in the association of insulin resistance with stroke risk: the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

BACKGROUND AND PURPOSE: Insulin resistance is associated with increased stroke risk, but the effect has not been adequately examined separately in white and black populations. METHODS: The association of baseline insulin resistance with risk of cerebral infarction (CI) and intracerebral hemorrhage (ICH) was assessed in 12 366 white and 6782 black participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, recruited between 2003 and 2007 and followed for an average of 5.7 years. Insulin resistance was measured with the homeostasis model assessment-insulin resistance. RESULTS: There were 364 incident CI and 41 incident ICH events. The risk for CI increased with the log of insulin resistance in whites (hazards ratio [HR]ln(IR)=1.17; 95% confidence interval [CI], 1.00-1.38) but was largely attenuated by adjustment for stroke risk factors (HRln(IR)=1.05; 95% CI, 0.88-1.26). There was no association in blacks (HRln(IR)=1.01; 95% CI, 0.81-1.25). After adjustment for demographic factors and risk factors, there was a significant difference by race in the association of insulin resistance with risk of ICH (P=0.07), with a decrease in the risk of ICH in whites (HRln(IR)=0.61; 95% CI, 0.35-1.04) but a nonsignificant increase in blacks (HRln(IR)=1.20; 95% CI, 0.60-2.39). CONCLUSIONS: These data support the growing evidence that insulin resistance may play a more important role in stroke risk among white than black individuals and suggest a potentially discordant relationship of insulin resistance on CI and ICH among whites.

Differences in ischemic and hemorrhagic recurrence rates among race-ethnic groups in the PRoFESS secondary stroke prevention trial.

BACKGROUND AND AIMS: Epidemiological studies show that vascular risk factors are the same across the world but their effect vary between different race-ethnic groups. However, few studies have evaluated differences in recurrent stroke rates in various race-ethnicities. In >20 000 patients spanning 35 countries encompassing most race-ethnicities, we evaluated the incidence of ischemic and hemorrhagic strokes and myocardial infarction in patients within the context of the largest secondary stroke prevention trial (Prevention Regimen for Effectively Avoiding Secondary Strokes) to identify any significant differences. METHODS: There were 20 332 patients with a recent ischemic stroke randomized in a factorial design to receive the antiplatelet agent clopidogrel vs. aspirin plus extended-release dipyridamole, and 80 mg of the anthypertensive telmisartan vs. placebo. The primary outcome for the trial was the time to any recurrent stroke. Statistical analysis was used to detect race-ethnic differences in recurrent vascular events. RESULTS: Mean patient age was 66 (±8·6) years and 36% were women. The study included 58% European/Caucasian, 33% Asians, 5% Latin/Hispanic, and 4% Black African. There were 74% of patients that were hypertensive, and average systolic and diastolic blood pressure was 144·1/83·8 mmHg. There was at least one significant difference in the overall test of all race-ethnic groups in myocardial infarction and symptomatic intracerebral hemorrhage occurrence. In the Kaplan-Meier hemorrhage and stroke-free survival curves, Asians showed a significantly higher recurrence of ischemic stroke risk in the 135-150 mmHg and greater than 150 mm Hg blood pressure groups, and a greater risk of hemorrhage recurrence in the greater than 150 mmHg blood pressure group. CONCLUSIONS: We found a significant difference in myocardial infarction and symptomatic intracerebral hemorrhage recurrence among different race-ethnic groups. The risk of recurrent ischemic and hemorrhagic stroke was greater in Asians with high blood pressure.

A blood-based biomarker panel to detect acute stroke.

BACKGROUND: The aim of this study was to develop an adjunctive, peripheral biomarker test to differentiate ischemic strokes, intracranial hemorrhages (ICHs), and stroke mimics in the acute setting. METHODS: Serum samples were collected from 167 patients who presented with an acute neurologic deficit within 24 hours of symptom onset. Patients were adjudicated to ischemic stroke, ICH, and mimic pathology groups based on clinical and radiographic findings. Samples were tested for levels of 262 potential markers. A multivariate Cox proportional hazards regression model of 5 biomarkers was built by stepwise selection and validated by bootstrapping. Its discriminative capacity was quantified by C index and net reclassification improvement (NRI). RESULTS: The final model consisted of eotaxin, epidermal growth factor receptor, S100A12, metalloproteinase inhibitor-4, and prolactin. It demonstrated a discriminative capacity for ischemic stroke versus mimic (C = .92), ischemic stroke and ICH versus mimic (C = .93), and ischemic stroke versus ICH (C = .82). The inclusion of biomarkers to a model consisting of age, race, and gender resulted in an NRI of 161% when detecting ischemic stroke versus mimic (P < .0001), an improvement of 171% when detecting ischemic strokes plus ICH versus mimic (P < .0001), and an improvement of 56% when detecting ischemic strokes versus ICH (P = .1419). CONCLUSIONS: These results suggest that information obtained from a 5-biomarker panel may add valuable information in the early evaluation and management of patients with stroke-like symptoms.

The iScore predicts clinical response to tissue plasminogen activator in Korean stroke patients.

BACKGROUND: Despite substantial differences in clinical features between Asian and Western stroke patients, there are no published prognostic tools validated in an Asiatic population for thrombolytic therapy. We assessed the ability of the iScore to predict the clinical response after intravenous thrombolysis with tissue plasminogen activator (tPA) in a Korean stroke population. METHODS: We applied the iScore to eligible participants in the nationwide multicenter stroke registry in Korea. Main outcome measures were poor functional outcome defined as having a modified Rankin Scale score 3-6 and death at 3 months. Symptomatic intracranial hemorrhage (sICH) was evaluated as a safety outcome. C statistic was calculated to assess performance of iScore. RESULTS: Among 4760 patients with an acute ischemic stroke, 622 (13.1%) received tPA, 548 patients had complete information for the analysis. C statistics for poor functional outcome and death at 3 months were .813 (95% confidence interval [CI]: .778-.848) and .820 (95% CI: .769-.872), respectively. Overall, there was a high correlation between observed and expected outcome for poor functional outcome (Pearson correlation coefficient, r = .982) and for death at 3 months (r = .950) at the risk score level. An iScore of 180 or more was associated with a more than 2 times risk of poor functional outcome and about 6 times risk of death at 3 months. There was an interaction between the iScore and tPA for a poor functional outcome (P value for the interaction < .001). We found a gradient effect in the incident risk of sICH with the iScore. CONCLUSION: The iScore reliably predicts stroke outcomes after tPA in Asiatic population.

Net clinical benefit of rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial fibrillation: a subgroup analysis of J-ROCKET AF.

BACKGROUND: The risk factors that have been identified for bleeding events with rivaroxaban are predominantly the same as those predicting thromboembolic ones in patients with atrial fibrillation (AF). Our aim was to determine the net clinical benefit (NCB) from the results of the J-ROCKET AF trial, in which rivaroxaban was compared with warfarin in Japanese patients with AF. METHODS: Two strategies were adopted to quantify the NCB. First, the NCB was calculated as the number of ischemic strokes avoided with anticoagulation minus the number of excess intracranial hemorrhage (ICH) with a weight of 1.5. Second, the composite end point of major bleeding events and secondary efficacy end points (stroke, noncentral nervous system systemic embolism, myocardial infarction and death) to ascertain the NCB were established. Subgroup analysis by CHADS2 score or creatinine clearance was also performed. RESULTS: The adjusted NCB, which was given a weight of 1.5 for ICH, was nominally significant in favor of rivaroxaban therapy (difference in incidence rate -2.13; 95% confidence interval [CI]: -.26 to -3.99). Furthermore, the event rate of the composite end point tended to be lower in patients treated with rivaroxaban than in those treated with warfarin (rivaroxaban: 4.97% per year, warfarin: 6.11% per year; difference in incidence rate: -1.14; 95% CI: -3.40 to 1.12). The event rate of the composite end point tended to be consistently low in patients treated with rivaroxaban in the subanalysis by CHADS2 score and renal function. CONCLUSION: Analysis of the NCB supports that rivaroxaban therapy provides clinical benefit for Japanese patients with AF.